The circadian clock is an important mechanism that links individual rhythm with external time. It can predict and respond to time, determine sleep-wake cycle, and participate in the regulation of circadian rhythms of various physiological behavior changes, including food intake and hormone balance in the body. The central circadian clock in mammals can regulate the peripheral circadian clocks of the gut, liver, and pancreas and other organs to maintain homeostasis and synchronize the operation of each organ, which can induce circadian changes in the structure, number, and colonization behavior of gut microbes by regulating feeding and sleep. Gut microbiota are the core part of intestinal microecology, which can regulate the physiology and functions of multiple organs and systems, including the brain, and have been proved to be the driving factors of the rhythmic expression of host clock molecules and a variety of circadian rhythm activities. In the past few years, the relationship between mammalian gut microbiota and circadian clock and their impact on diseases have been partially revealed, but further research is still needed to explore the specific mechanism of their cooperation in the context of human diseases. This paper reviews the current research progress on the bidirectional regulation between mammalian circadian clock and gut microbiota and the specific molecular mechanisms involved, hoping to provide new interventions and therapeutic targets for the treatment of diseases.